ANX7 as a Bio‐Marker in Prostate and Breast Cancer Progression

Srivastava, Meera; Bubendorf, Lukas; Nolan, Lisa K.; Glasman, Mirta; Leighton, Ximena; Miller, Georgina; Fehrle, Wilfred; Eidelman, Ofer; Kallioniemi, Olli; Srivastava, Shiv; Pollard, Harvey B.

doi:10.1155/2001/239602

Cited by 33 publications

(25 citation statements)

References 34 publications

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“…Altered ANXA7 expression was associated with advanced stage and probability of survival in the prostate and breast cancers with metastases and hormone refractoriness. 6,8,10 Additionally, we found a significant allelic loss of ANXA7 region in the estrogen and progesterone hormone receptor negative breast carcinomas indicating ANXA7 associations with hormonal dysregulation in cancer. 9 To elucidate ANXA7 role in hormone-relevant carcinogenesis, we undertook a study on profiling of ANXA7 in human tumors in comparison to NKX3.1, a steroid-regulated transcription factor and biomarker that is mostly associated with male genitalia tumorigenesis but can be also found in lobular breast carcinoma.…”

mentioning

confidence: 55%

“…[6][7][8] Samples were scored as ANXA7-or NKX3.1-positive based on intensity and uniformity of nuclear/cytoplasmic staining. Diaminobenzidine was used as a chromagen for protein detection.…”

Section: Tissue Microarraysmentioning

confidence: 99%

“…6 Concordantly, Anxa7(1/2) heterozygote mice exhibited tendency to develop a spectrum of tumors in addition to profound genderdimorphic gigantism and organomegaly. 7 Our recent studies 6,8,9 indicated that ANXA7 can be a biomarker in the progression of cancer derived from 2 hormone-relevant and gender-specific tissues -prostate and breast. Altered ANXA7 expression was associated with advanced stage and probability of survival in the prostate and breast cancers with metastases and hormone refractoriness.…”

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confidence: 99%

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ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

Srivastava

Torosyan

Raffeld

et al. 2007

Intl Journal of Cancer

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Tumor suppressor function of ubiquitously expressed Annexin-A7, ANXA7 (10q21) that is involved in exocytosis and membrane fusion was based on cancer prone phenotype in Anxa7(1/2) mice as well as ANXA7 role in human prostate and breast cancers. To clarify ANXA7 biomarker and tumor suppressor function, we analyzed its expression pattern in comparison to the prostate-specific biomarker NKX3.1. Immunohistochemistry-based ANXA7 and NKX3.1 protein expression was analyzed on human tissue microarrays of 4,061 specimens from a wide spectrum of the histopathologically well-characterized tumors in different stages compared to corresponding normal tissues. Decreased ANXA7 expression was mostly associated with high invasive potential in multiple tumors. Although some metastases retained relatively high ANXA7 rates compared to primary cancer tissues, the lymph node metastases from different sites (including prostate and breast) had decreased ANXA7 expression in comparison to the intact lymphatic tissues. Major ANXA7 downregulation pattern was deviated in tumors of glandular (especially neuroendocrine) origin. ANXA7 and NKX3.1 proteins were synexpressed in the male urogenital system and adrenal gland. Gene expression profiling in prostate and breast cancers (SMD) revealed distinct hormone-related profiles for NKX3.1 and ANXA7, where ANXA7 expression correlated with steroid sulfatase which has a pivotal role in steroidogenesis. Abundant protein presence in adrenal gland and its loss in hormone-refractory prostate cancer indicated that ANXA7 can be relevant to steroidogenesis and androgen sensitivity in particular. With tumor suppressor pattern validated in different tumors, ANXA7 can be an attractive diagnostic and therapeutic target associated with the hormone and/or neurotransmitter-mediated modulation of tumorigenesis. ' 2007 Wiley-Liss, Inc.

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confidence: 55%

Section: Tissue Microarraysmentioning

confidence: 99%

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confidence: 99%

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ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

Srivastava

Torosyan

Raffeld

et al. 2007

Intl Journal of Cancer

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“…The classic bacterial derived FPR-1 ligand, fMLP, has also been shown to activate FPRL-1, albeit with significantly reduced affinity (79). Other infectious agent-derived agonists include human immunodeficiency virus, type 1 envelope proteins and the Helicobacter pylori peptide Hp (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). WKYMVm is an agonist for all three nFPR family members that were derived from peptide libraries (80,81).…”

Section: Discussionmentioning

confidence: 99%

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

Babbin

Lee

Parkos

et al. 2006

Journal of Biological Chemistry

132

141

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“…Although the homozygous Anx7(Ϫ͞Ϫ) deletion is embryonically lethal, the phenotype of the Anx7(ϩ͞Ϫ) heterozygote includes calcium signaling deficits and growth defects such as gigantism, and selective organomegaly. As these mice aged, we also began to observe a profoundly increased frequency of disparate spontaneous tumors in both male and female Anx7(ϩ͞Ϫ) mutants (17).…”

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confidence: 98%

ANX7, a candidate tumor suppressor gene for prostate cancer

Srivastava

Bubendorf

Srikantan

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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The ANX7 gene is located on human chromosome 10q21, a site long hypothesized to harbor a tumor suppressor gene(s) (TSG) associated with prostate and other cancers. To test whether ANX7 might be a candidate TSG, we examined the ANX7-dependent suppression of human tumor cell growth, stage-specific ANX7 expression in 301 prostate specimens on a prostate tissue microarray, and loss of heterozygosity (LOH) of microsatellite markers at or near the ANX7 locus. Here we report that human tumor cell proliferation and colony formation are markedly reduced when the wild-type ANX7 gene is transfected into two prostate tumor cell lines, LNCaP and DU145. Consistently, analysis of ANX7 protein expression in human prostate tumor microarrays reveals a significantly higher rate of loss of ANX7 expression in metastatic and local recurrences of hormone refractory prostate cancer as compared with primary tumors (P ‫؍‬ 0.0001). Using four microsatellite markers at or near the ANX7 locus, and laser capture microdissected tumor cells, 35% of the 20 primary prostate tumors show LOH. The microsatellite marker closest to the ANX7 locus showed the highest rate of LOH, including one homozygous deletion. We conclude that the ANX7 gene exhibits many biological and genetic properties expected of a TSG and may play a role in prostate cancer progression.cancer genetics ͉ chromosome 10q21 ͉ loss of heterozygosity T he gene for annexin 7 (ANX7 ‡ ‡ , synexin; refs. 1-6) is located on human chromosome 10q21, where potential tumor suppressor genes (TSGs) have been hypothesized to exist for prostate and other cancers (5, 7-15). However, the specific relevance of the ANX7 gene for cancer only became apparent after we created a knockout for this gene in the mouse (16). Although the homozygous Anx7(Ϫ͞Ϫ) deletion is embryonically lethal, the phenotype of the Anx7(ϩ͞Ϫ) heterozygote includes calcium signaling deficits and growth defects such as gigantism, and selective organomegaly. As these mice aged, we also began to observe a profoundly increased frequency of disparate spontaneous tumors in both male and female Anx7(ϩ͞Ϫ) mutants (17).Because of these observations, and the chromosomal location of the gene, we hypothesized that ANX7 might be a candidate TSG associated with 10q21 locus. Commonly, TSGs can suppress growth of tumor cells, in vitro, and are frequently inactivated by mutations, deletions, or loss of expression in tumors, in vivo. In addition, loss of heterozygosity (LOH) often is observed for these genes in clinical tumor specimens. Therefore, to test this hypothesis for the ANX7 gene, we analyzed the action of the ANX7 gene on colony formation by human tumor cell lines. We also examined the expression of the ANX7 protein in hundreds of prostate cancers by using tumor tissue microarray technology. Finally, we tested a panel of primary and metastatic prostate cancers for evidence of LOH.In this paper we show that the ANX7 gene suppresses the growth of the prostate tumor cell lines DU145 and LNCaP. Consistently, in a prostate tissue microarray, we...

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ANX7 as a Bio‐Marker in Prostate and Breast Cancer Progression

Cited by 33 publications

References 34 publications

ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

ANXA7 expression represents hormone‐relevant tumor suppression in different cancers

Annexin I Regulates SKCO-15 Cell Invasion by Signaling through Formyl Peptide Receptors

ANX7, a candidate tumor suppressor gene for prostate cancer

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